Activation of the Nuclear Factor κB Pathway by Astrocyte Elevated Gene-1: Implications for Tumor Progression and Metastasis

作者: Luni Emdad , Devanand Sarkar , Zao-zhong Su , Aaron Randolph , Habib Boukerche

DOI: 10.1158/0008-5472.CAN-05-3029

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摘要: Astrocyte elevated gene-1 (AEG-1) was initially identified as an HIV-1- and tumor necrosis factor α (TNF-α)–inducible transcript in primary human fetal astrocytes by a rapid subtraction hybridization approach. Interestingly, AEG-1 expression is subsets of breast cancer, glioblastoma multiforme melanoma cells cooperates with Ha-ras to promote transformation immortalized melanocytes. Activation the transcription nuclear κB (NF-κB), TNF-α downstream signaling component, associated several illnesses, including NF-κB controls multiple genes involved progression metastasis. We now document that significant positive regulator NF-κB. Enhanced via replication-incompetent adenovirus (Ad.AEG-1) HeLa markedly increased binding transcriptional activator p50/p65 complex The activation induced corresponded degradation IκBα translocation p65 resulted induction genes. Infection expressing mt32IκBα superrepressor (Ad.IκBα-mt32), which prevents translocation, inhibited AEG-1-induced enhanced agar cloning efficiency matrigel invasion cells. also treatment both wherein these two proteins physically interacted, suggesting potential mechanism could activate Our findings suggest represent key molecular promotes anchorage-independent growth invasion, central features neoplastic phenotype. (Cancer Res 2006; 66(3): 1509-16)

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